CLN3

CLN3 lysosomal/endosomal transmembrane protein, battenin

Basic information

Region (hg38): 16:28474111-28495575

Previous symbols: [ "BTS" ]

Links

ENSG00000188603 ∙ NCBI:1201 ∙ OMIM:607042 ∙ HGNC:2074 ∙ Uniprot:Q13286 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neuronal ceroid lipofuscinosis 3 (Definitive), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 3 (Definitive), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 3 (Strong), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 3 (Definitive), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 3 (Supportive), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 3 (Strong), mode of inheritance: AR
• neuronal ceroid lipofuscinosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ceroid lipofuscinosis, neuronal, 3	AR	Neurologic	Levodopa treatment may be beneficial	Biochemical; Neurologic; Ophthalmologic	7426545; 1609833; 1319116; 7553855; 7887420; 9004140; 9311735; 9450775; 10477428; 11342698; 15965709; 17947292; 19135632; 19489875; 21990111

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLN3 gene.

• Neuronal ceroid lipofuscinosis (38 variants)
• Neuronal ceroid lipofuscinosis 3 (25 variants)
• not provided (11 variants)
• Retinitis pigmentosa (3 variants)
• Inborn genetic diseases (2 variants)
• Cone-rod dystrophy (2 variants)
• Ceroid lipofuscinosis, neuronal, 3, protracted (1 variants)
• early onset and severe retinal dystrophy (1 variants)
• Retinal dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLN3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	210	1	213
missense	1	10	269	20		300
nonsense	10	21		1		32
start loss	1	2				3
frameshift	26	29	2	1		58
inframe indel			5			5
splice donor/acceptor (+/-2bp)	7	41	1			49
splice region	1	4	22	65	5	97
non coding	1		15	198	21	235
Total	46	103	294	430	22

Highest pathogenic variant AF is 0.0000197

Variants in CLN3

This is a list of pathogenic ClinVar variants found in the CLN3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-28477311-C-T		Neuronal Ceroid-Lipofuscinosis, Dominant/Recessive • Neuronal ceroid lipofuscinosis 3	Uncertain significance (Jan 13, 2018)
16-28477316-T-C		Neuronal Ceroid-Lipofuscinosis, Dominant/Recessive • Neuronal ceroid lipofuscinosis 3	Uncertain significance (Jan 12, 2018)
16-28477329-C-T		Neuronal ceroid lipofuscinosis 3	Uncertain significance (Jan 12, 2018)
16-28477361-T-G		Neuronal ceroid lipofuscinosis 3	Likely benign (Jun 23, 2018)
16-28477405-C-A		Neuronal ceroid lipofuscinosis 3	Uncertain significance (Apr 27, 2017)
16-28477417-G-A		Neuronal Ceroid-Lipofuscinosis, Dominant/Recessive • Neuronal ceroid lipofuscinosis 3	Conflicting classifications of pathogenicity (Jul 08, 2018)
16-28477438-C-T		Neuronal Ceroid-Lipofuscinosis, Dominant/Recessive • Neuronal ceroid lipofuscinosis 3	Uncertain significance (Jan 13, 2018)
16-28477458-T-G		Neuronal ceroid lipofuscinosis 3	Uncertain significance (Mar 23, 2018)
16-28477461-G-T		Neuronal Ceroid-Lipofuscinosis, Dominant/Recessive • Neuronal ceroid lipofuscinosis 3	Uncertain significance (Jan 13, 2018)
16-28477487-T-C		Neuronal Ceroid-Lipofuscinosis, Dominant/Recessive • Neuronal ceroid lipofuscinosis 3	Uncertain significance (Jan 13, 2018)
16-28477517-C-T		Neuronal ceroid lipofuscinosis	Likely benign (Mar 30, 2020)
16-28477524-G-A			Uncertain significance (Apr 17, 2017)
16-28477528-G-C		Neuronal ceroid lipofuscinosis • Inborn genetic diseases	Uncertain significance (Oct 25, 2022)
16-28477531-G-T		Neuronal ceroid lipofuscinosis	Likely benign (Dec 20, 2022)
16-28477540-A-G		Neuronal ceroid lipofuscinosis	Likely benign (May 02, 2023)
16-28477542-G-A		Neuronal ceroid lipofuscinosis	Uncertain significance (Aug 28, 2021)
16-28477545-G-A		Neuronal ceroid lipofuscinosis	Likely benign (Jan 29, 2024)
16-28477548-G-A		Neuronal ceroid lipofuscinosis • Neuronal ceroid lipofuscinosis 3	Uncertain significance (Aug 23, 2022)
16-28477549-C-T		Neuronal ceroid lipofuscinosis	Likely benign (Dec 05, 2023)
16-28477557-G-C		Neuronal ceroid lipofuscinosis	Uncertain significance (Sep 11, 2021)
16-28477560-GC-G		Neuronal ceroid lipofuscinosis 3	Likely pathogenic (-)
16-28477561-C-T		Neuronal ceroid lipofuscinosis	Likely benign (Sep 17, 2020)
16-28477564-C-T		Neuronal ceroid lipofuscinosis • Inborn genetic diseases	Likely benign (Dec 11, 2023)
16-28477565-G-A		Retinitis pigmentosa • Neuronal ceroid lipofuscinosis	Uncertain significance (Sep 17, 2021)
16-28477565-G-T		Neuronal ceroid lipofuscinosis 3	Likely pathogenic (May 28, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLN3	protein_coding	protein_coding	ENST00000569430	15	28914

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.33e-7	0.951	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.146	255	249	1.03	0.0000154	2766
Missense in Polyphen		106	105.85	1.0015		1281
Synonymous	-1.08	129	114	1.13	0.00000767	946
Loss of Function	1.93	15	25.5	0.588	0.00000122	283

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000956	0.0000462
European (Non-Finnish)	0.000205	0.000202
Middle Eastern	0.000218	0.000217
South Asian	0.000132	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in microtubule-dependent, anterograde transport of late endosomes and lysosomes. {ECO:0000269|PubMed:22261744}.
• Disease: DISEASE: Ceroid lipofuscinosis, neuronal, 3 (CLN3) [MIM:204200]: A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The hallmark of CLN3 is the ultrastructural pattern of lipopigment with a fingerprint profile, which can have 3 different appearances: pure within a lysosomal residual body; in conjunction with curvilinear or rectilinear profiles; and as a small component within large membrane-bound lysosomal vacuoles. The combination of fingerprint profiles within lysosomal vacuoles is a regular feature of blood lymphocytes from patients with neuronal ceroid lipofuscinosis type 3. {ECO:0000269|PubMed:21990111, ECO:0000269|PubMed:22261744, ECO:0000269|PubMed:9311735, ECO:0000269|PubMed:9490299}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.284

Intolerance Scores

• loftool: 0.231
• rvis_EVS: -0.16
• rvis_percentile_EVS: 42.16

Haploinsufficiency Scores

• pHI: 0.376
• hipred: N
• hipred_score: 0.146
• ghis: 0.534

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.900

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cln3
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype

Zebrafish Information Network

• Gene name: cln3
• Affected structure: neuron
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: action potential;globoside metabolic process;cellular amino acid metabolic process;ceramide metabolic process;glucosylceramide metabolic process;galactosylceramide metabolic process;sphingomyelin metabolic process;receptor-mediated endocytosis;lysosome organization;lysosomal lumen acidification;associative learning;arginine transport;macroautophagy;protein processing;protein catabolic process;ionotropic glutamate receptor signaling pathway;lysosomal lumen pH elevation;neurotransmitter metabolic process;amyloid precursor protein catabolic process;negative regulation of apoptotic process;negative regulation of catalytic activity;negative regulation of neuron apoptotic process;negative regulation of proteolysis;vesicle transport along microtubule;neuromuscular process controlling balance;regulation of intracellular pH;regulation of cytosolic calcium ion concentration;membrane organization;autophagosome maturation
• Cellular component: Golgi membrane;nucleus;cytoplasm;mitochondrion;lysosome;lysosomal membrane;early endosome;late endosome;autophagosome;endoplasmic reticulum;Golgi apparatus;Golgi stack;trans-Golgi network;plasma membrane;caveola;synaptic vesicle;integral component of membrane;integral component of endoplasmic reticulum membrane;neuron projection;membrane raft
• Molecular function: protein binding;unfolded protein binding